Escherichia coli K-12 substr. MG1655 Enzyme: isovaleryl-CoA dehydrogenase and DNA-binding transcriptional repressor

Gene: aidB Accession Numbers: EG11811 (EcoCyc), b4187, ECK4183

Regulation Summary Diagram: ?

Regulation summary diagram for aidB

Subunit composition of isovaleryl-CoA dehydrogenase and DNA-binding transcriptional repressor = [AidB]4

AidB is a multifunctional protein that forms part of E.coli's adaptive response to alkylating agents as defined by the ada regulon. The biological role of AidB is not clear - the purified protein has low levels of isovaleryl-CoA dehydrogenase activity, displays DNA binding activity and can negatively regulate its own expression in vivo.

Apo AidB has a high affinity for flavin adenine dinucleotide (FAD), which helps with the assembly of the AidB tetramer [Hamill11]. AidB was overexpressed, purified, and found to contain a FAD cofactor in stoichiometric quantities [Rohankhedkar06]. The purified protein has a very low level of isovaleryl-CoA dehydrogenase activity and binds double-stranded DNA with a preference for methylated and/or relaxed DNA [Rohankhedkar06]. In in vitro binding experiments AidB shows preferential binding to a DNA region that includes the upstream sequence and -35 box of its own promoter [Rippa10]. AidB can repress its own synthesis during normal cell growth [Rippa10]. The crystal structure of AidB has been determined [Bowles08, Hamill11]. The purified N-terminal region of AidB (residues 1-439) has isovaleryl-CoA dehydrogenase activity but cannot bind DNA; the purified C-terminal region (residues 440-540) can bind DNA and functions as a transcriptional repressor in vivo but does not show isovaleryl-CoA dehydrogenase activity [Rippa10].

Overexpression of the aidB gene results in increased isovaleryl-CoA dehydrogenase activity in cell extracts [Landini94]. Overexpression also results in mutation rates which are less-than-wild-type after MNNG treatment [Landini94]. Some aidB lac fusions are less sensitive to alkylation damage than wild type [Volkert84, Volkert86]. An aidB mutant shows a wild-type adaptive response to alkylation treatment [Volkert84] and a wild-type adaptive response to H2O2 treatment with respect to protection against subsequent MNNG-induced damage [Asad97].

Expression of aidB is regulated by Ada in response to alkylation damage (primarily methylation) and involves interaction with RNA polymerase sigma factor Eσ70 or EσS [Volkert84, Volkert86, Volkert89, Landini94, Landini95, Landini95a, Landini98, Landini99, Lacour02, Lacour03]. Based on lac fusion experiments, expression ofaidB is induced by treatment with methyl methanesulfonate, MNNG, streptozotocin, and N-methyl-N-nitrosourea and shows growth phase regulation which is independent of ada [Volkert84, Fram88]. Gene expression is induced under conditions of anaerobiosis [Volkert89a] or acidification with acetate [Smirnova94] and is dependent upon RpoS in these cases [Volkert94]. Lrp is a repressor of aidB expression [Landini96]. cysA mutants block anaerobic induction of aidB while cysD, cysN, cysC, or cysH mutations increase anaerobic induction of aidB [Matijasevic92]. aidB was induced by treatment with the sulfhydryl reagent N-ethylmaleimide [Smirnova94].

AidB has similarity to acyl coenzyme A dehydrogenases from mammals [Landini94].

Reviews: [Volkert88, Landini00, Sedgwick02, Janion06].

AidB: "alkylation-inducible" [Volkert84].

Citations: [Vasileva05]

Locations: cytosol

Map Position: [4,412,298 -> 4,413,923] (95.1 centisomes, 342°)
Length: 1626 bp / 541 aa

Molecular Weight of Polypeptide: 60.59 kD (from nucleotide sequence), 56.0 kD (experimental) [Landini94 ]

Molecular Weight of Multimer: 200.0 kD (experimental) [Rohankhedkar06]

Unification Links: ASAP:ABE-0013701 , CGSC:18553 , DIP:DIP-9078N , EchoBASE:EB1759 , EcoGene:EG11811 , EcoliWiki:b4187 , Mint:MINT-1221527 , ModBase:P33224 , OU-Microarray:b4187 , PDB:3DJL , PortEco:aidB , PR:PRO_000022072 , Pride:P33224 , Protein Model Portal:P33224 , RefSeq:NP_418608 , RegulonDB:EG11811 , SMR:P33224 , String:511145.b4187 , UniProt:P33224

Relationship Links: InterPro:IN-FAMILY:IPR006089 , InterPro:IN-FAMILY:IPR006091 , InterPro:IN-FAMILY:IPR009075 , InterPro:IN-FAMILY:IPR009100 , PDB:Structure:3U33 , Pfam:IN-FAMILY:PF00441 , Pfam:IN-FAMILY:PF02770 , Prosite:IN-FAMILY:PS00072 , Prosite:IN-FAMILY:PS00073

In Paralogous Gene Group: 335 (3 members)

Gene-Reaction Schematic: ?

Gene-Reaction Schematic

Genetic Regulation Schematic: ?

Genetic regulation schematic for aidB

GO Terms:

Biological Process: GO:0006974 - cellular response to DNA damage stimulus Inferred from experiment [Volkert84]
GO:0045892 - negative regulation of transcription, DNA-templated Inferred from experiment [Rippa10]
GO:0008152 - metabolic process Inferred by computational analysis [GOA01a]
GO:0055114 - oxidation-reduction process Inferred by computational analysis [UniProtGOA11a, GOA01a]
Molecular Function: GO:0003677 - DNA binding Inferred from experiment Inferred by computational analysis [UniProtGOA11a, Rohankhedkar06]
GO:0005515 - protein binding Inferred from experiment [Bowles08]
GO:0008470 - isovaleryl-CoA dehydrogenase activity Inferred from experiment [Rohankhedkar06]
GO:0043565 - sequence-specific DNA binding Inferred from experiment [Rippa10]
GO:0003995 - acyl-CoA dehydrogenase activity Inferred by computational analysis [GOA01a]
GO:0016491 - oxidoreductase activity Inferred by computational analysis [UniProtGOA11a]
GO:0016627 - oxidoreductase activity, acting on the CH-CH group of donors Inferred by computational analysis [GOA01a]
Cellular Component: GO:0005737 - cytoplasm Inferred by computational analysis [UniProtGOA11, UniProtGOA11a]

MultiFun Terms: regulation type of regulation transcriptional level repressor

Symmetry: Inverted Repeat

Regulated Transcription Units (1 total): ?


Transcription-unit diagram

Essentiality data for aidB knockouts: ?

Growth Medium Growth? T (°C) O2 pH Osm/L Growth Observations
LB enriched Yes 37 Aerobic 6.95   Yes [Gerdes03, Comment 1]
LB Lennox Yes 37 Aerobic 7   Yes [Baba06, Comment 2]
M9 medium with 1% glycerol Yes 37 Aerobic 7.2 0.35 Yes [Joyce06, Comment 3]
MOPS medium with 0.4% glucose Yes 37 Aerobic 7.2 0.22 Yes [Baba06, Comment 2]

Created 13-May-2008 by Johnson A , JCVI
Curated 03-Nov-2010 by Mackie A , Macquarie University
Last-Curated ? 05-Nov-2010 by Santos-Zavaleta A , UNAM

Enzymatic reaction of: isovaleryl-CoA dehydrogenase

Synonyms: isovaleryl-coenzyme A dehydrogenase, 3-methylbutanoyl-CoA:(acceptor) oxidoreductase, AidB

EC Number:

isovaleryl-CoA + an oxidized electron-transfer flavoprotein + H+ <=> 3-methylcrotonyl-CoA + a reduced electron-transfer flavoprotein

The reaction direction shown, that is, A + B ↔ C + D versus C + D ↔ A + B, is in accordance with the Enzyme Commission system.

Reversibility of this reaction is unspecified.

Overexpression of the aidB gene results in increased isovaleryl coenzyme A dehydrogenase activity in cell extracts [Landini94]. A low level of isovaleryl-CoA dehydrogenase activity of purified AidB has been demonstrated [Rohankhedkar06].

Sequence Features

Protein sequence of AidB with features indicated

Feature Class Location Attached Group Citations Comment
Catalytic-Domain 2 -> 439  
isovaleryl-CoA dehydrogenase activity
Nucleotide-Phosphate-Binding-Region 182 -> 191 FAD
[Bowles08, UniProt15]
UniProt: FAD.
Amino-Acid-Sites-That-Bind 185  
[Bowles08, UniProt15]
UniProt: FAD.
Amino-Acid-Sites-That-Bind 191  
[Bowles08, UniProt15]
UniProt: FAD.
Nucleotide-Phosphate-Binding-Region 216 -> 218 FAD
[Bowles08, UniProt15]
UniProt: FAD.
Amino-Acid-Sites-That-Bind 218  
[Bowles08, UniProt15]
UniProt: FAD.
Nucleotide-Phosphate-Binding-Region 423 -> 433 FAD
[Bowles08, UniProt15]
UniProt: FAD.
Amino-Acid-Sites-That-Bind 429  
[Bowles08, UniProt15]
UniProt: FAD.
Mutagenesis-Variant 437  
[Bowles08, UniProt11]
UniProt: Does not affect DNA binding affinity.
DNA-Binding-Region 440 -> 541  
Protein-Segment 445 -> 541  
UniProt: dsDNA-binding; Sequence Annotation Type: region of interest.
Mutagenesis-Variant 518  
[Bowles08, UniProt11]
UniProt: Reduces DNA binding affinity.

Gene Local Context (not to scale): ?

Gene local context diagram

Transcription Unit:

Transcription-unit diagram


Peter D. Karp on Wed Jan 18, 2006:
Gene left-end position adjusted based on analysis performed in the 2005 E. coli annotation update [Riley06 ].
10/20/97 Gene b4187 from Blattner lab Genbank (v. M52) entry merged into EcoCyc gene EG11811; confirmed by SwissProt match.


Asad97: Asad LM, Asad NR, Silva AB, Felzenszwalb I, Leitao AC (1997). "Hydrogen peroxide induces protection against N-methyl-N'-nitro-N-nitrosoguanidine (MNNG) effects in Escherichia coli." Mutat Res 383(2);137-42. PMID: 9088346

Baba06: Baba T, Ara T, Hasegawa M, Takai Y, Okumura Y, Baba M, Datsenko KA, Tomita M, Wanner BL, Mori H (2006). "Construction of Escherichia coli K-12 in-frame, single-gene knockout mutants: the Keio collection." Mol Syst Biol 2;2006.0008. PMID: 16738554

Bowles08: Bowles T, Metz AH, O'Quin J, Wawrzak Z, Eichman BF (2008). "Structure and DNA binding of alkylation response protein AidB." Proc Natl Acad Sci U S A 105(40);15299-304. PMID: 18829440

Fram88: Fram RJ, Marinus MG, Volkert MR (1988). "Gene expression in E. coli after treatment with streptozotocin." Mutat Res 198(1);45-51. PMID: 2965298

Gerdes03: Gerdes SY, Scholle MD, Campbell JW, Balazsi G, Ravasz E, Daugherty MD, Somera AL, Kyrpides NC, Anderson I, Gelfand MS, Bhattacharya A, Kapatral V, D'Souza M, Baev MV, Grechkin Y, Mseeh F, Fonstein MY, Overbeek R, Barabasi AL, Oltvai ZN, Osterman AL (2003). "Experimental determination and system level analysis of essential genes in Escherichia coli MG1655." J Bacteriol 185(19);5673-84. PMID: 13129938

GOA01a: GOA, DDB, FB, MGI, ZFIN (2001). "Gene Ontology annotation through association of InterPro records with GO terms."

Hamill11: Hamill MJ, Jost M, Wong C, Elliott SJ, Drennan CL (2011). "Flavin-induced oligomerization in Escherichia coli adaptive response protein AidB." Biochemistry 50(46);10159-69. PMID: 22004173

Janion06: Janion C (2006). "[Chemically methylated DNA repair in Escherichia coli--the role of alkB protein]." Postepy Biochem 52(3);239-46. PMID: 17201058

Joyce06: Joyce AR, Reed JL, White A, Edwards R, Osterman A, Baba T, Mori H, Lesely SA, Palsson BO, Agarwalla S (2006). "Experimental and computational assessment of conditionally essential genes in Escherichia coli." J Bacteriol 188(23);8259-71. PMID: 17012394

Lacour02: Lacour S, Kolb A, Boris Zehnder AJ, Landini P (2002). "Mechanism of specific recognition of the aidB promoter by sigma(S)-RNA polymerase." Biochem Biophys Res Commun 292(4);922-30. PMID: 11944903

Lacour03: Lacour S, Kolb A, Landini P (2003). "Nucleotides from -16 to -12 determine specific promoter recognition by bacterial sigmaS-RNA polymerase." J Biol Chem 278(39);37160-8. PMID: 12853450

Landini00: Landini P, Volkert MR (2000). "Regulatory responses of the adaptive response to alkylation damage: a simple regulon with complex regulatory features." J Bacteriol 182(23);6543-9. PMID: 11073893

Landini94: Landini P, Hajec LI, Volkert MR (1994). "Structure and transcriptional regulation of the Escherichia coli adaptive response gene aidB." J Bacteriol 176(21);6583-9. PMID: 7961409

Landini95: Landini P, Volkert MR (1995). "Transcriptional activation of the Escherichia coli adaptive response gene aidB is mediated by binding of methylated Ada protein. Evidence for a new consensus sequence for Ada-binding sites." J Biol Chem 1995;270(14);8285-9. PMID: 7713936

Landini95a: Landini P, Volkert MR (1995). "RNA polymerase alpha subunit binding site in positively controlled promoters: a new model for RNA polymerase-promoter interaction and transcriptional activation in the Escherichia coli ada and aidB genes." EMBO J 14(17);4329-35. PMID: 7556074

Landini96: Landini P, Hajec LI, Nguyen LH, Burgess RR, Volkert MR (1996). "The leucine-responsive regulatory protein (Lrp) acts as a specific repressor for sigma s-dependent transcription of the Escherichia coli aidB gene." Mol Microbiol 20(5);947-55. PMID: 8809748

Landini98: Landini P, Bown JA, Volkert MR, Busby SJ (1998). "Ada protein-RNA polymerase sigma subunit interaction and alpha subunit-promoter DNA interaction are necessary at different steps in transcription initiation at the Escherichia coli Ada and aidB promoters." J Biol Chem 273(21);13307-12. PMID: 9582376

Landini99: Landini P, Busby SJ (1999). "The Escherichia coli Ada protein can interact with two distinct determinants in the sigma70 subunit of RNA polymerase according to promoter architecture: identification of the target of Ada activation at the alkA promoter." J Bacteriol 181(5);1524-9. PMID: 10049384

Matijasevic92: Matijasevic Z, Hajec LI, Volkert MR (1992). "Anaerobic induction of the alkylation-inducible Escherichia coli aidB gene involves genes of the cysteine biosynthetic pathway." J Bacteriol 174(6);2043-6. PMID: 1312537

Riley06: Riley M, Abe T, Arnaud MB, Berlyn MK, Blattner FR, Chaudhuri RR, Glasner JD, Horiuchi T, Keseler IM, Kosuge T, Mori H, Perna NT, Plunkett G, Rudd KE, Serres MH, Thomas GH, Thomson NR, Wishart D, Wanner BL (2006). "Escherichia coli K-12: a cooperatively developed annotation snapshot--2005." Nucleic Acids Res 34(1);1-9. PMID: 16397293

Rippa10: Rippa V, Amoresano A, Esposito C, Landini P, Volkert M, Duilio A (2010). "Specific DNA binding and regulation of its own expression by the AidB protein in Escherichia coli." J Bacteriol 192(23);6136-42. PMID: 20889740

Rohankhedkar06: Rohankhedkar MS, Mulrooney SB, Wedemeyer WJ, Hausinger RP (2006). "The AidB component of the Escherichia coli adaptive response to alkylating agents is a flavin-containing, DNA-binding protein." J Bacteriol 188(1);223-30. PMID: 16352838

Sedgwick02: Sedgwick B, Lindahl T (2002). "Recent progress on the Ada response for inducible repair of DNA alkylation damage." Oncogene 21(58);8886-94. PMID: 12483506

Smirnova94: Smirnova GV, Oktyabrsky ON, Moshonkina EV, Zakirova NV (1994). "Induction of the alkylation-inducible aidB gene of Escherichia coli by cytoplasmic acidification and N-ethylmaleimide." Mutat Res 314(1);51-6. PMID: 7504191

UniProt11: UniProt Consortium (2011). "UniProt version 2011-06 released on 2011-06-30 00:00:00." Database.

UniProt15: UniProt Consortium (2015). "UniProt version 2015-01 released on 2015-01-16 00:00:00." Database.

UniProtGOA11: UniProt-GOA (2011). "Gene Ontology annotation based on the manual assignment of UniProtKB Subcellular Location terms in UniProtKB/Swiss-Prot entries."

UniProtGOA11a: UniProt-GOA (2011). "Gene Ontology annotation based on manual assignment of UniProtKB keywords in UniProtKB/Swiss-Prot entries."

Vasileva05: Vasil'eva SV, Moshkovskaia EIu (2005). "[Quasi-adaptive response to alkylating agents in Escherichia coli: a new phenomenon]." Genetika 41(5);607-13. PMID: 15977811

Volkert84: Volkert MR, Nguyen DC (1984). "Induction of specific Escherichia coli genes by sublethal treatments with alkylating agents." Proc Natl Acad Sci U S A 81(13);4110-4. PMID: 6330740

Volkert86: Volkert MR, Nguyen DC, Beard KC (1986). "Escherichia coli gene induction by alkylation treatment." Genetics 112(1);11-26. PMID: 3080354

Volkert88: Volkert MR (1988). "Adaptive response of Escherichia coli to alkylation damage." Environ Mol Mutagen 11(2);241-55. PMID: 3278898

Volkert89: Volkert MR, Gately FH, Hajec LI (1989). "Expression of DNA damage-inducible genes of Escherichia coli upon treatment with methylating, ethylating and propylating agents." Mutat Res 217(2);109-15. PMID: 2493133

Volkert89a: Volkert MR, Hajec LI, Nguyen DC (1989). "Induction of the alkylation-inducible aidB gene of Escherichia coli by anaerobiosis." J Bacteriol 171(2);1196-8. PMID: 2492508

Volkert94: Volkert MR, Hajec LI, Matijasevic Z, Fang FC, Prince R (1994). "Induction of the Escherichia coli aidB gene under oxygen-limiting conditions requires a functional rpoS (katF) gene." J Bacteriol 176(24);7638-45. PMID: 8002588

Other References Related to Gene Regulation

Maciag11: Maciag A, Peano C, Pietrelli A, Egli T, De Bellis G, Landini P (2011). "In vitro transcription profiling of the {sigma}S subunit of bacterial RNA polymerase: re-definition of the {sigma}S regulon and identification of {sigma}S-specific promoter sequence elements." Nucleic Acids Res 39(13);5338-55. PMID: 21398637

Vasilieva10: Vasilieva SV, Streltsova DA, Moshkovskaya EY, Sanina NA, Aldoshin SM (2010). "Fnr[4Fe-4S](2+) protein regulates the aidB gene expression in Escherichia coli cultured under anaerobic conditions." Dokl Biochem Biophys 433;179-82. PMID: 20714851

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Please cite the following article in publications resulting from the use of EcoCyc: Nucleic Acids Research 41:D605-12 2013
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